Disease relevance of Tnr

• TN-R deficient mice showed motor coordination impairments in the wire hanging, Rotarod and pole test [1].
• The extracellular matrix molecule tenascin-R (TN-R), predominantly expressed in the central nervous system, has been implied in a variety of functions, e.g. during myelination, cerebellar neurite fasciculation and hippocampal long-term potentiation [2].
• When janusin and tenascin were offered as sharp substrate boundaries, dorsal root ganglion (DRG) and retinal ganglion neuron growth cones avoided growing on these molecules, but were not induced to collapse [3].
• We conclude that divalent metal ions stabilize the association of TN-R with CNS myelin and upon damage, the protein can be released and degraded by endogenous proteases, suggesting the implication of myelin-derived TN-R in axon growth inhibition and demyelinating diseases [4].

High impact information on Tnr

• Tenascin-C, tenascin-R and tenascin-X: a family of talented proteins in search of functions [5].
• Tenascin-R mediates activity-dependent recruitment of neuroblasts in the adult mouse forebrain [6].
• Tenascin-R is an intrinsic autocrine factor for oligodendrocyte differentiation and promotes cell adhesion by a sulfatide-mediated mechanism [7].
• In the absence of platelet-derived growth factor (PDGF), exogenous TN-R induced myelin gene expression and the upregulation of its own synthesis by cultured cells, resulting in a rapid terminal differentiation of O4(+) progenitors [7].
• At the molecular level this process was mediated by protein binding to membrane surface sulfatides (Sulf), as indicated by the interference of O4 antibody and Sulf with the attachment of OLs or other Sulf+ cells, erythrocytes, to TN-R substrates and by direct protein-glycolipid binding studies [7].

Biological context of Tnr

• Isolation of a tenascin-R binding protein from mouse brain membranes. A phosphacan-related chondroitin sulfate proteoglycan [8].
• Differential effects of the mutations on whisking were found: recovery of function was worse in TNC-deficient and better in TNR null mice compared with wild-type littermates [9].
• As previously reported, tenascin-R is prominently expressed in subcortical white matter, and we found it was not expressed in the barrel boundaries in any of the genotypes [10].
• Neuronal-specific synthesis and glycosylation of tenascin-R [11].
• The present study examined electroencephalograms (EEGs) and auditory-evoked potentials (AEPs) in freely moving TN-R-/- and wild-type control mice, focusing on the hippocampal CA1 field and cerebral cortex [12].

Anatomical context of Tnr

• Co-localization of the molecule with TN-R in the retina and optic nerve by immunocytochemistry suggests a functional relationship between the two molecules in vivo [8].
• Inhibition of neurite outgrowth from hippocampal neurons by the phosphacan-related molecule in vitro is neutralized by TN-R when coated as a uniform substrate [8].
• Furthermore, the phosphacan-related molecule neutralizes growth cone repulsion induced by TN-R coated as a sharp substrate boundary with or without prior treatment with chondroitinase ABC [8].
• To test this hypothesis, we investigated adult mice constitutively deficient in the expression of TNC, TNR or both, using the facial nerve injury paradigm [9].
• Reduced extracellular space in the brain of tenascin-R- and HNK-1-sulphotransferase deficient mice [13].

Associations of Tnr with chemical compounds

• Enhanced cortical and hippocampal neuronal excitability in mice deficient in the extracellular matrix glycoprotein tenascin-R [12].
• In order to test whether the revealed abnormalities give rise to increased susceptibility to seizures in TN-R-deficient mice, we used the pilocarpine model of epilepsy [14].
• Tenascin-R interferes with integrin-dependent oligodendrocyte precursor cell adhesion by a ganglioside-mediated signalling mechanism [15].
• Using culture conditions that allow the isolation of mouse OLs at distinct lineage stages, here we demonstrate that TN-R is antiadhesive for GD3+ preOLs and inhibits their integrin-dependent adhesion to fibronectin (FN) by a disialoganglioside-mediated signalling mechanism affecting the tyrosine phosphorylation of the focal adhesion kinase [15].
• Our previous electrophysiologic study of mice deficient in the extracellular matrix glycoprotein tenascin-R (TN-R) showed an impaired gamma-aminobutyric acid release at perisomatic inhibitory synapses in the CA1 pyramidal cell layer of the hippocampus [16].

Physical interactions of Tnr

• These observations indicate that TN-R can interact with a phosphacan-related molecule and thereby modulate its inhibitory influence on neuritogenesis [8].
• The possibility that these O -glycans enable tenascin-R to interact in the CNS either with the myelin associated glycoprotein or with sialoadhesin on activated microglia is discussed [17].

Regulatory relationships of Tnr

• Our results provide strong evidence that TNC promotes and TNR impedes recovery after nerve lesion [9].

Other interactions of Tnr

• These findings reveal alterations in ST-/- mice that differ from EEG abnormalities of mice deficient in the HNK-1 carrier molecule tenascin-R [18].
• Morphology of perineuronal nets in tenascin-R and parvalbumin single and double knockout mice [19].
• Binding of the phosphacan-related molecule to the epidermal growth factor-like repeats of TN-R is Ca2+-dependent [8].
• We conclude that the lack of TN-R initially and continuously disturbs the molecular scaffolding of extracellular matrix components in perineuronal nets [20].
• In addition, tenascin-R 180 and tenascin-C interact with cells by an RGD- and beta 1 integrin-independent mechanism, leading to cell rounding and detachment from such substrata [21].

Analytical, diagnostic and therapeutic context of Tnr

• TN-R-/- mice expressed normal high-frequency oscillations (ripples) in CA1 and only a slight reduction of peak theta frequency [12].
• TN-R transcripts in adult mouse brain contain non-coding exons 1 and 2 as demonstrated by the reverse transcriptase-polymerase chain reaction [22].
• Assignment of the tenascin-R gene (Tnr) to mouse chromosome 4 band E2 by fluorescence in situ hybridization; refinement of the human TNR location to chromosome 1q24 [23].
• In cell cultures of young postnatal mouse or rat optic nerves, oligodendrocytes and type-2 astrocytes, but not type-1 astrocytes were stained by janusin antibodies [24].
• Expression of janusin was influenced by co-culture with astrocytes or neurons [25].

References